tbuckley/cabot-search huggingface dataset:
Reduction of Lung Hyperinflation Improves Cardiac Preload, Contractility, and Output in Emphysema: A Clinical Trial in Patients Who Received Endobronchial Valves
Authors: Marieke C. van der Molen, Jorine E. Hartman, Lowie E. G. W. Vanfleteren, Huib A. M. Kerstjens, Joost P. van Melle, Tineke P. Willems, Dirk-Jan Slebos
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: Pulmonary hyperinflation in patients with chronic obstructive pulmonary disease has been related to smaller cardiac chamber sizes and impaired cardiac function. Currently, bronchoscopic lung volume reduction (BLVR) with endobronchial valves is a treatment option to reduce pulmonary hyperinflation in patients with severe emphysema. Objectives: We hypothesized that reduction of hyperinflation would improve cardiac preload in this patient group. In addition, we investigated whether the treatment would result in elevated pulmonary artery pressures because of pulmonary vascular bed reduction. Methods: We included patients with emphysema and severe hyperinflation (defined by a baseline residual volume >175% of predicted) who were eligible for BLVR with endobronchial valves. Cardiac magnetic resonance imaging was obtained one day before treatment and at 8-week follow-up. Primary endpoint was cardiac preload, as measured by the right ventricle end-diastolic volume index. As secondary endpoints, we measured indexed end-diastolic and end-systolic volumes of the right ventricle, left atrium, and left ventricle; pulmonary artery pressures; cardiac output; ejection fraction; and strain. Measurements and Main Results: Twenty-four patients were included. At 8-week follow-up, right ventricle end-diastolic volume index was significantly improved (+7.9 ml/m2; SD, 10.0; P = 0.001). In addition to increased stroke volumes, we found significantly higher ejection fractions and strain measurements. Although cardiac output was significantly increased (+0.9 L/min; SD, 1.5; P = 0.007), there were no changes in pulmonary artery pressures. Conclusions: We found that reduction of hyperinflation using BLVR with endobronchial valves significantly improved cardiac preload, myocardial contractility, and cardiac output, without changes in pulmonary artery pressures. Clinical trial registered with www.clinicaltrials.gov (NCT03474471).
Gene-based therapeutics for rare genetic neurodevelopmental psychiatric disorders
Authors: Beverly L. Davidson, Guangping Gao, Elizabeth Berry-Kravis, Allison M. Bradbury, Carsten Bönnemann, Joseph D. Buxbaum, Gavin R. Corcoran, Steven J. Gray, Heather Gray-Edwards, Robin J. Kleiman, Adam J. Shaywitz, Dan Wang, Huda Y. Zoghbi, Terence R. Flotte, Sitra Tauscher-Wisniewski, Cynthia J. Tifft, Mustafa Sahin
Journal: Molecular Therapy (2022)

We are in an emerging era of gene-based therapeutics with significant promise for rare genetic disorders. The potential is particularly significant for genetic central nervous system disorders that have begun to achieve Food and Drug Administration approval for select patient populations. This review summarizes the discussions and presentations of the National Institute of Mental Health-sponsored workshop "Gene-Based Therapeutics for Rare Genetic Neurodevelopmental Psychiatric Disorders," which was held in January 2021. Here, we distill the points raised regarding various precision medicine approaches related to neurodevelopmental and psychiatric disorders that may be amenable to gene-based therapies. We are in an emerging era of gene-based therapeutics with significant promise for rare genetic disorders. The potential is particularly significant for genetic central nervous system disorders that have begun to achieve Food and Drug Administration approval for select patient populations. This review summarizes the discussions and presentations of the National Institute of Mental Health-sponsored workshop "Gene-Based Therapeutics for Rare Genetic Neurodevelopmental Psychiatric Disorders," which was held in January 2021. Here, we distill the points raised regarding various precision medicine approaches related to neurodevelopmental and psychiatric disorders that may be amenable to gene-based therapies.
Correction: Cerebrospinal fluid tau levels are associated with abnormal neuronal plasticity markers in Alzheimer’s disease
Authors: Pieter Jelle Visser, Lianne M. Reus, Johan Gobom, Iris Jansen, Ellen Dicks, Sven J. van der Lee, Magda Tsolaki, Frans R. J. Verhey, Julius Popp, Pablo Martinez-Lage, Rik Vandenberghe, Alberto Lleó, José Luís Molinuevo, Sebastiaan Engelborghs, Yvonne Freund-Levi, Lutz Froelich, Kristel Sleegers, Valerija Dobricic, Simon Lovestone, Johannes Streffer, Stephanie J. B. Vos, Isabelle Bos, August B. Smit, Kaj Blennow, Philip Scheltens, Charlotte E. Teunissen, Lars Bertram, Henrik Zetterberg, Betty M. Tijms, August B. Smit, Kaj Blennow, Philip Scheltens, Charlotte E. Teunissen, Lars Bertram, Henrik Zetterberg, Betty M. Tijms
Journal: Molecular Neurodegeneration (2022)
Use of Sewage Surveillance for COVID-19: A Large-Scale Evidence-Based Program in Hong Kong
Authors: Yu Deng, Xiawan Zheng, Xiaoqing Xu, Ho-kwong Chui, Wai-kwan Lai, Shuxian Li, Hein Min Tun, Leo L.M. Poon, Jiahui Ding, Malik Peiris, Gabriel M. Leung, Tong Zhang
Journal: Environmental Health Perspectives (2022)

Sewage surveillance, by detecting SARS-CoV-2 virus circulation at the community level, has the potential to supplement individual surveillance for COVID-19. However, to date, there have been no reports about the large-scale implementation and validation of sewage surveillance for public health action.
Genetically proxied ketohexokinase function and risk of colorectal cancer: a Mendelian randomisation study
Authors: Amée M Buziau, Philip J Law, Gabriella Blokland, Casper Schalkwijk, Jean Scheijen, Pomme Simons, Carla van der Kallen, Simone Eussen, Pieter C Dagnelie, Marleen van Greevenbroek, Richard S Houlston, Anke Wesselius, Molly Went, Coen Stehouwer, Martijn CGJ Brouwers
Journal: Gut (2022)
Aβ oligomer concentration in mouse and human brain and its drug-induced reduction ex vivo
Authors: Bettina Kass, Sarah Schemmert, Christian Zafiu, Marlene Pils, Oliver Bannach, Janine Kutzsche, Tuyen Bujnicki, Dieter Willbold
Journal: Cell Reports Medicine (2022)

The elimination of amyloid beta (Aβ) oligomers is a promising strategy for therapeutic drug development of Alzheimer's disease (AD). AD mouse models that develop Aβ pathology have been used to demonstrate in vivo efficacy of compounds that later failed in clinical development. Here, we analyze the concentration and size distribution of Aβ oligomers in different transgenic mouse models of AD and in human brain samples by surface-based fluorescence intensity distribution analysis (sFIDA), a highly sensitive method for detecting and quantitating protein aggregates. We demonstrate dose- and time-dependent oligomer elimination by the compound RD2 in mouse and human AD brain homogenates as sources of native Aβ oligomers. Such ex vivo target engagement analyses with mouse- and human-brain-derived oligomers have the potential to enhance the translational value from pre-clinical proof-of-concept studies to clinical trials.
Navigating financial toxicity in patients with cancer: A multidisciplinary management approach
Authors: Grace L. Smith, Matthew P. Banegas, Chiara Acquati, Shine Chang, Fumiko Chino, Rena M. Conti, Rachel A. Greenup, Juliet L. Kroll, Margaret I. Liang, Maria Pisu, Kristin M. Primm, Michael E. Roth, Veena Shankaran, K. Robin Yabroff
Journal: CA A Cancer Journal for Clinicians (2022)

Abstract Approximately one‐half of individuals with cancer face personal economic burdens associated with the disease and its treatment, a problem known as financial toxicity (FT). FT more frequently affects socioeconomically vulnerable individuals and leads to subsequent adverse economic and health outcomes. Whereas multilevel systemic factors at the policy, payer, and provider levels drive FT, there are also accompanying intervenable patient‐level factors that exacerbate FT in the setting of clinical care delivery. The primary strategy to intervene on FT at the patient level is financial navigation . Financial navigation uses comprehensive assessment of patients’ risk factors for FT, guidance toward support resources, and referrals to assist patient financial needs during cancer care. Social workers or nurse navigators most frequently lead financial navigation. Oncologists and clinical provider teams are multidisciplinary partners who can support optimal FT management in the context of their clinical roles. Oncologists and clinical provider teams can proactively assess patient concerns about the financial hardship and employment effects of disease and treatment. They can respond by streamlining clinical treatment and care delivery planning and incorporating FT concerns into comprehensive goals of care discussions and coordinated symptom and psychosocial care. By understanding how age and life stage, socioeconomic, and cultural factors modify FT trajectory, oncologists and multidisciplinary health care teams can be engaged and informative in patient‐centered, tailored FT management. The case presentations in this report provide a practical context to summarize authors’ recommendations for patient‐level FT management, supported by a review of key supporting evidence and a discussion of challenges to mitigating FT in oncology care. CA Cancer J Clin. 2022;72:437‐453.
Factors Associated With Serological Response to SARS-CoV-2 Vaccination in Patients With Multiple Sclerosis Treated With Rituximab
Authors: Andreas Tolf, Anna Wiberg, Malin Müller, Faisal Hayat Nazir, Ivan Pavlovic, Ida Laurén, Sara Mangsbo, Joachim Burman
Journal: JAMA Network Open (2022)

B-cell-depleting monoclonal antibodies are widely used for treatment of multiple sclerosis but are associated with an impaired response to vaccines.To identify factors associated with a favorable vaccine response to tozinameran.This prospective cohort study was conducted in a specialized multiple sclerosis clinic at a university hospital from January 21 to December 1, 2021. Of 75 patients evaluated for participation who received a diagnosis of multiple sclerosis with planned or ongoing treatment with rituximab, 69 were included in the study, and data from 67 were analyzed.Sex, age, number of previous rituximab infusions, accumulated dose of rituximab, previous COVID-19 infection, time since last rituximab treatment, CD19+ B-cell count before vaccination, CD4+ T-cell count, and CD8+ T-cell count were considered potential factors associated with the main outcome.Serological vaccine responses were measured by quantitation of anti-spike immunoglobulin G (IgG) antibodies, anti-receptor-binding domain (RBD) IgG antibodies, and their neutralizing capacities. Cellular responses to spike protein-derived SARS-CoV-2 peptide pools were assessed by counting interferon gamma spot-forming units in a FluoroSpot assay.Among 60 patients with ongoing rituximab treatment (49 women [82%]; mean (SD) age, 43 [10] years), the median (range) disease duration was 9 (1-29) years, and the median (range) dose of rituximab was 2750 (500-10 000) mg during a median (range) time of 2.8 (0.5-8.3) years. The median (range) follow-up from the first vaccination dose was 7.3 (4.3-10.0) months. Vaccine responses were determined before vaccination with tozinameran and 6 weeks after vaccination. By using established cutoff values for anti-spike IgG (264 binding antibody units/mL) and anti-RBD IgG (506 binding antibody units/mL), the proportion of patients with a positive response increased with the number of B cells, which was the only factor associated with these outcomes. A cutoff for the B-cell count of at least 40/μL was associated with an optimal serological response. At this cutoff, 26 of 29 patients (90%) had positive test results for anti-spike IgG and 21 of 29 patients (72%) for anti-RBD IgG, and 27 of 29 patients (93%) developed antibodies with greater than 90% inhibition of angiotensin-converting enzyme 2. No factor associated with the cellular response was identified. Depending on the peptide pool, 21 of 25 patients (84%) to 22 of 25 patients (88%) developed a T-cell response with interferon gamma production at the B-cell count cutoff of at least 40/μL.This cohort study found that for an optimal vaccine response from tozinameran, rituximab-treated patients with multiple sclerosis may be vaccinated as soon as possible, with rituximab treatment delayed until B-cell counts have reached at least 40/μL. An additional vaccination with tozinameran should be considered at that point.
Artificial intelligence-assisted optical diagnosis for the resect-and-discard strategy in clinical practice: the Artificial intelligence BLI Characterization (ABC) study
Authors: Emanuele Rondonotti, Cesare Hassan, Giacomo Tamanini, Giulio Antonelli, Gianluca Andrisani, Giovanni Leonetti, Silvia Paggi, Arnaldo Amato, Giulia Scardino, Dhanai Di Paolo, Giovanna Mandelli, Nicoletta Lenoci, Natalia Terreni, Alida Andrealli, Roberta Maselli, Marco Spadaccini, Piera Alessia Galtieri, Loredana Correale, Alessandro Repici, Francesco Maria Di Matteo, Luciana Ambrosiani, Emanuela Filippi, Prateek Sharma, Franco Radaelli
Journal: Endoscopy (2022)

Optical diagnosis of colonic polyps is poorly reproducible outside of high volume referral centers. The present study aimed to assess whether real-time artificial intelligence (AI)-assisted optical diagnosis is accurate enough to implement the leave-in-situ strategy for diminutive (≤ 5 mm) rectosigmoid polyps (DRSPs).Consecutive colonoscopy outpatients with ≥ 1 DRSP were included. DRSPs were categorized as adenomas or nonadenomas by the endoscopists, who had differing expertise in optical diagnosis, with the assistance of a real-time AI system (CAD-EYE). The primary end point was ≥ 90 % negative predictive value (NPV) for adenomatous histology in high confidence AI-assisted optical diagnosis of DRSPs (Preservation and Incorporation of Valuable endoscopic Innovations [PIVI-1] threshold), with histopathology as the reference standard. The agreement between optical- and histology-based post-polypectomy surveillance intervals (≥ 90 %; PIVI-2 threshold) was also calculated according to European Society of Gastrointestinal Endoscopy (ESGE) and United States Multi-Society Task Force (USMSTF) guidelines.Overall 596 DRSPs were retrieved for histology in 389 patients; an AI-assisted high confidence optical diagnosis was made in 92.3 %. The NPV of AI-assisted optical diagnosis for DRSPs (PIVI-1) was 91.0 % (95 %CI 87.1 %-93.9 %). The PIVI-2 threshold was met with 97.4 % (95 %CI 95.7 %-98.9 %) and 92.6 % (95 %CI 90.0 %-95.2 %) of patients according to ESGE and USMSTF, respectively. AI-assisted optical diagnosis accuracy was significantly lower for nonexperts (82.3 %, 95 %CI 76.4 %-87.3 %) than for experts (91.9 %, 95 %CI 88.5 %-94.5 %); however, nonexperts quickly approached the performance levels of experts over time.AI-assisted optical diagnosis matches the required PIVI thresholds. This does not however offset the need for endoscopists' high level confidence and expertise. The AI system seems to be useful, especially for nonexperts.
Abstract A018: Lung cancer associated DNA Damageome reveals a genome destabilizing role of Aquaporin 3
Authors: Jun Xia, Mu Lin, Zhuoyi Song, Gail Fernandes, Susan Rosenberg, Chris Amos
Journal: Cancer Research (2022)

Abstract Lung cancer is a multifactorial disease caused by both environmental exposures and genetic factors. Genome and transcriptome-wide association studies (GWAS and TWAS) successfully identified many genetic variants and candidate causal genes associated with lung cancer. However, the lack of functional studies of these genes remains a major bottleneck to clinical translation. Recently, we discovered that large networks of evolutionarily conserved DNA damageome proteins (DDPs) promote DNA damage and genome instability. Here, we discovered a lung cancer-associated DNA damageome network. We further discovered that one of the lung cancer DDPs, Aquaporin 3 (AQP3), can promote ROS dependent DNA damage upon overproduction. Furthermore, it potentiates DNA damage by a low dose of arsenic exposure, creating unique double strand break hotspots which help predict mutational signatures. We screened for high endogenous DNA damage levels for more than 40 TWAS and GWAS-nominated candidates using high-throughput single cell-based flow cytometric assays. We optimized and performed Mre11-Cut&amp;Tag (Cleavage Under Targets and Tagmentation) to map double strand breaks, which are the most deleterious form of DNA damage. In addition, we used END-Seq to provide a much higher resolution of the DSB map and uncovered hotspots in arsenic-detoxifying genes. We are implementing duplex sequencing to map the mutational signatures caused by arsenic and the arsenic-Aquaporin 3 interaction. Our study brings function to endogenous DNA damage and DNA damageome proteins that interact with environmental toxicants. Mechanistic insights into how low-dose arsenic interacts with risk genes yield critical knowledge for the prevention, diagnosis, and treatment of arsenic-associated diseases. We also uncovered several early biomarkers to potentially predict the long-term health impacts of arsenic. Citation Format: Jun Xia, Mu Lin, Zhuoyi Song, Gail Fernandes, Susan Rosenberg, Chris Amos. Lung cancer associated DNA Damageome reveals a genome destabilizing role of Aquaporin 3 [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr A018.
Combination of acitretin and narrowband UV-B for the treatment of vitiligo: A new treatment modality with an impact on tissue E-cadherin expression
Authors: Shahira Ramadan, Ola Abu Zeid, Samia Esmat, Noha Adly Saleh, Magda Assaf, Rana Fathy Hilal
Journal: Journal of the American Academy of Dermatology (2022)
Application of an infrared thermography-based model to detect pressure injuries: a prospective cohort study
Authors: Xiaoqiong Jiang, Yu Wang, Yuxin Wang, Min Zhou, Pan Huang, Yufan Yang, Fang Peng, Haishuang Wang, Xiaomei Li, Liping Zhang, Fuman Cai
Journal: British Journal of Dermatology (2022)

It is challenging to detect pressure injuries at an early stage of their development.To assess the ability of an infrared thermography (IRT)-based model, constructed using a convolution neural network, to reliably detect pressure injuries.A prospective cohort study compared validity in patients with pressure injury (n = 58) and without pressure injury (n = 205) using different methods. Each patient was followed up for 10 days.The optimal cut-off values of the IRT-based model were 0·53 for identifying tissue damage 1 day before visual detection of pressure injury and 0·88 for pressure injury detection on the day visual detection is possible. Kaplan-Meier curves and Cox proportional hazard regression model analysis showed that the risk of pressure injury increased 13-fold 1 day before visual detection with a cut-off value higher than 0·53 [hazard ratio (HR) 13·04, 95% confidence interval (CI) 6·32-26·91; P < 0·001]. The ability of the IRT-based model to detect pressure injuries [area under the receiver operating characteristic curve (AUC)lag 0 days , 0·98, 95% CI 0·95-1·00] was better than that of other methods.The IRT-based model is a useful and reliable method for clinical dermatologists and nurses to detect pressure injuries. It can objectively and accurately detect pressure injuries 1 day before visual detection and is therefore able to guide prevention earlier than would otherwise be possible. What is already known about this topic? Detection of pressure injuries at an early stage is challenging. Infrared thermography can be used for the physiological and anatomical evaluation of subcutaneous tissue abnormalities. A convolutional neural network is increasingly used in medical imaging analysis. What does this study add? The optimal cut-off values of the IRT-based model were 0·53 for identifying tissue damage 1 day before visual detection of pressure injury and 0·88 for pressure injury detection on the day visual detection is possible. Infrared thermography-based models can be used by clinical dermatologists and nurses to detect pressure injuries at an early stage objectively and accurately.
Blood phospho-tau in Alzheimer disease: analysis, interpretation, and clinical utility
Authors: Thomas K. Karikari, Nicholas J. Ashton, Gunnar Brinkmalm, Wagner S. Brum, Andréa L. Benedet, Laia Montoliu-Gaya, Juan Lantero-Rodriguez, Tharick Ali Pascoal, Marc Suárez-Calvet, Pedro Rosa-Neto, Kaj Blennow, Henrik Zetterberg
Journal: Nature Reviews Neurology (2022)
Single anastomosis sleeve jejunal (SAS-J) bypass as a treatment for morbid obesity, technique and review of 1986 cases and 6 Years follow-up. Retrospective cohort
Authors: Alaa M. Sewefy, Ahmed M. Atyia, Mohammed M. Mohammed, Taha H. Kayed, Hosam M. Hamza
Journal: International Journal of Surgery (2022)
Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial
Authors: Francois-Clement Bidard, Virginia G. Kaklamani, Patrick Neven, Guillermo Streich, Alberto J. Montero, Frédéric Forget, Marie-Ange Mouret-Reynier, Joo Hyuk Sohn, Donatienne Taylor, Kathleen K. Harnden, Hung Khong, Judit Kocsis, Florence Dalenc, Patrick M. Dillon, Sunil Babu, Simon Waters, Ines Deleu, José A. García Sáenz, Emilio Bria, Marina Cazzaniga, Janice Lu, Philippe Aftimos, Javier Cortés, Shubin Liu, Giulia Tonini, Dirk Laurent, Nassir Habboubi, Maureen G. Conlan, Aditya Bardia
Journal: Journal of Clinical Oncology (2022)

Patients with pretreated estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer have poor prognosis. Elacestrant is a novel, oral selective ER degrader that demonstrated activity in early studies.